JP2013533864A5 - - Google Patents
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- JP2013533864A5 JP2013533864A5 JP2013515513A JP2013515513A JP2013533864A5 JP 2013533864 A5 JP2013533864 A5 JP 2013533864A5 JP 2013515513 A JP2013515513 A JP 2013515513A JP 2013515513 A JP2013515513 A JP 2013515513A JP 2013533864 A5 JP2013533864 A5 JP 2013533864A5
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- Prior art keywords
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- seq
- amino acid
- Prior art date
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 26
- 125000000217 alkyl group Chemical group 0.000 claims 23
- 235000001014 amino acid Nutrition 0.000 claims 21
- 150000001413 amino acids Chemical class 0.000 claims 21
- 229940024606 amino acid Drugs 0.000 claims 20
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 14
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 13
- 235000004279 alanine Nutrition 0.000 claims 13
- 229960003767 alanine Drugs 0.000 claims 13
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 11
- 235000013922 glutamic acid Nutrition 0.000 claims 11
- 229960002989 glutamic acid Drugs 0.000 claims 11
- 239000004220 glutamic acid Substances 0.000 claims 11
- 239000004026 insulin derivative Substances 0.000 claims 11
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 10
- 229960002743 glutamine Drugs 0.000 claims 9
- 239000004475 Arginine Substances 0.000 claims 8
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims 8
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims 8
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims 8
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 8
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims 8
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims 8
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims 8
- 239000004473 Threonine Substances 0.000 claims 8
- 235000009697 arginine Nutrition 0.000 claims 8
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 8
- 229960003121 arginine Drugs 0.000 claims 8
- 125000003118 aryl group Chemical group 0.000 claims 8
- 235000003704 aspartic acid Nutrition 0.000 claims 8
- 229960005261 aspartic acid Drugs 0.000 claims 8
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims 8
- 235000014304 histidine Nutrition 0.000 claims 8
- 229960002885 histidine Drugs 0.000 claims 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 8
- 229960003104 ornithine Drugs 0.000 claims 8
- 239000000651 prodrug Substances 0.000 claims 8
- 229940002612 prodrug Drugs 0.000 claims 8
- 235000008521 threonine Nutrition 0.000 claims 8
- 229960002898 threonine Drugs 0.000 claims 8
- 229960004441 tyrosine Drugs 0.000 claims 8
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims 8
- 235000002374 tyrosine Nutrition 0.000 claims 8
- 239000004471 Glycine Substances 0.000 claims 7
- 102000004877 Insulin Human genes 0.000 claims 7
- 108090001061 Insulin Proteins 0.000 claims 7
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 7
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims 7
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 7
- 239000004472 Lysine Substances 0.000 claims 7
- 150000001412 amines Chemical group 0.000 claims 7
- 125000004429 atom Chemical group 0.000 claims 7
- 235000004554 glutamine Nutrition 0.000 claims 7
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims 7
- 229960002449 glycine Drugs 0.000 claims 7
- 229910052739 hydrogen Inorganic materials 0.000 claims 7
- 229940125396 insulin Drugs 0.000 claims 7
- 235000018977 lysine Nutrition 0.000 claims 7
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 7
- 229960005190 phenylalanine Drugs 0.000 claims 7
- 235000008729 phenylalanine Nutrition 0.000 claims 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 6
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims 6
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 6
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims 6
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 6
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 6
- 235000014705 isoleucine Nutrition 0.000 claims 6
- 229960000310 isoleucine Drugs 0.000 claims 6
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims 6
- 235000005772 leucine Nutrition 0.000 claims 6
- 229960003136 leucine Drugs 0.000 claims 6
- 235000006109 methionine Nutrition 0.000 claims 6
- 229930182817 methionine Natural products 0.000 claims 6
- 229960004452 methionine Drugs 0.000 claims 6
- 235000004400 serine Nutrition 0.000 claims 6
- 229960001153 serine Drugs 0.000 claims 6
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims 5
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims 5
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 5
- 239000000556 agonist Substances 0.000 claims 5
- 235000009582 asparagine Nutrition 0.000 claims 5
- 229960001230 asparagine Drugs 0.000 claims 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 5
- 239000001257 hydrogen Substances 0.000 claims 5
- 229960003646 lysine Drugs 0.000 claims 5
- 229960002429 proline Drugs 0.000 claims 5
- 235000013930 proline Nutrition 0.000 claims 5
- 235000014393 valine Nutrition 0.000 claims 5
- 229960004295 valine Drugs 0.000 claims 5
- 239000004474 valine Substances 0.000 claims 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- 239000002202 Polyethylene glycol Substances 0.000 claims 3
- -1 aromatic amino acid Chemical class 0.000 claims 3
- 125000003827 glycol group Chemical group 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 229920001223 polyethylene glycol Polymers 0.000 claims 3
- CMUHFUGDYMFHEI-QMMMGPOBSA-N 4-amino-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N)C=C1 CMUHFUGDYMFHEI-QMMMGPOBSA-N 0.000 claims 2
- 108010016626 Dipeptides Proteins 0.000 claims 2
- GEYBMYRBIABFTA-UHFFFAOYSA-N O-methyltyrosine Chemical compound COC1=CC=C(CC(N)C(O)=O)C=C1 GEYBMYRBIABFTA-UHFFFAOYSA-N 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 210000004899 c-terminal region Anatomy 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 238000006467 substitution reaction Methods 0.000 claims 2
- QCKMEYKASJTMKI-ILCMOUOISA-N 2-aminoacetic acid;(2s)-2-aminopentanedioic acid;(2s)-pyrrolidine-2-carboxylic acid Chemical compound NCC(O)=O.OC(=O)[C@@H]1CCCN1.OC(=O)[C@@H](N)CCC(O)=O QCKMEYKASJTMKI-ILCMOUOISA-N 0.000 claims 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- VBOQYPQEPHKASR-VKHMYHEASA-N L-homocysteic acid Chemical compound OC(=O)[C@@H](N)CCS(O)(=O)=O VBOQYPQEPHKASR-VKHMYHEASA-N 0.000 claims 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- AUTOLBMXDDTRRT-UHFFFAOYSA-N dethiobiotin Chemical compound CC1NC(=O)NC1CCCCCC(O)=O AUTOLBMXDDTRRT-UHFFFAOYSA-N 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 239000000539 dimer Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 150000001261 hydroxy acids Chemical class 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 230000004962 physiological condition Effects 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 229960004799 tryptophan Drugs 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35536610P | 2010-06-16 | 2010-06-16 | |
| US61/355,366 | 2010-06-16 | ||
| US201161433500P | 2011-01-17 | 2011-01-17 | |
| US61/433,500 | 2011-01-17 | ||
| PCT/US2011/040699 WO2011159895A2 (en) | 2010-06-16 | 2011-06-16 | Single chain insulin agonists exhibiting high activity at the insulin receptor |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013533864A JP2013533864A (ja) | 2013-08-29 |
| JP2013533864A5 true JP2013533864A5 (https=) | 2014-08-07 |
| JP5969469B2 JP5969469B2 (ja) | 2016-08-17 |
Family
ID=45348866
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013515513A Expired - Fee Related JP5969469B2 (ja) | 2010-06-16 | 2011-06-16 | インスリン受容体に対して高い活性を示す単鎖インスリンアゴニスト |
Country Status (7)
| Country | Link |
|---|---|
| US (3) | US8940860B2 (https=) |
| EP (1) | EP2582719B1 (https=) |
| JP (1) | JP5969469B2 (https=) |
| CN (1) | CN103068842B (https=) |
| AU (1) | AU2011268327B2 (https=) |
| CA (1) | CA2802485C (https=) |
| WO (1) | WO2011159895A2 (https=) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2009210570B2 (en) | 2008-01-30 | 2014-11-20 | Indiana University Research And Technology Corporation | Ester-based insulin prodrugs |
| JP5912112B2 (ja) | 2010-06-24 | 2016-04-27 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ | アミド系インスリンプロドラッグ |
| US9573987B2 (en) | 2011-12-20 | 2017-02-21 | Indiana University Research And Technology Corporation | CTP-based insulin analogs for treatment of diabetes |
| AU2013323669B2 (en) * | 2012-09-26 | 2018-03-01 | Indiana University Research And Technology Corporation | Insulin analog dimers |
| US9707276B2 (en) | 2012-12-03 | 2017-07-18 | Merck Sharp & Dohme Corp. | O-glycosylated carboxy terminal portion (CTP) peptide-based insulin and insulin analogues |
| TR201910929T4 (tr) * | 2013-02-26 | 2019-08-21 | Hanmi Pharm Ind Co Ltd | Bölgeye özel insülin konjugatı. |
| WO2014158900A1 (en) | 2013-03-14 | 2014-10-02 | Indiana University Research And Technology Corporation | Insulin-incretin conjugates |
| GB201321489D0 (en) * | 2013-12-05 | 2014-01-22 | Chemical & Biopharmaceutical Lab Of Patras S A | Biologically active insulin derivatives |
| EP3098235A4 (en) * | 2014-01-20 | 2017-10-18 | Hanmi Pharm. Co., Ltd. | Long-acting insulin and use thereof |
| WO2016049174A1 (en) | 2014-09-24 | 2016-03-31 | Indiana University Research And Technology Corporation | Lipidated amide-based insulin prodrugs |
| ES2822994T3 (es) | 2014-09-24 | 2021-05-05 | Univ Indiana Res & Tech Corp | Conjugados de incretina-insulina |
| AU2015328222B9 (en) | 2014-10-06 | 2020-12-24 | Case Western Reserve University | Biphasic single-chain insulin analogues |
| EA036714B1 (ru) | 2014-11-21 | 2020-12-10 | Мерк Шарп И Доум Корп. | Частичные агонисты инсулинового рецептора |
| JP6914844B2 (ja) * | 2015-03-13 | 2021-08-04 | ケース ウェスタン リザーブ ユニバーシティＣａｓｅ Ｗｅｓｔｅｒｎ Ｒｅｓｅｒｖｅ Ｕｎｉｖｅｒｓｉｔｙ | グルコース制御立体配座スイッチを含むインスリン類似体 |
| AR105616A1 (es) | 2015-05-07 | 2017-10-25 | Lilly Co Eli | Proteínas de fusión |
| CN104805091B (zh) * | 2015-05-13 | 2018-01-30 | 武汉真福医药股份有限公司 | 重组人胰岛素的表达方法及专用表达载体、工程菌和应用 |
| UY36870A (es) * | 2015-08-28 | 2017-03-31 | Hanmi Pharm Ind Co Ltd | Análogos de insulina novedosos |
| WO2017180988A2 (en) | 2016-04-15 | 2017-10-19 | Indiana University Research And Technology Corporation | Fgf21 c-terminal peptide optimization |
| EP3448417B1 (en) | 2016-04-26 | 2025-11-12 | Merck Sharp & Dohme LLC | Insulin dimer-incretin conjugates |
| EP3463429A4 (en) | 2016-05-24 | 2020-07-22 | Merck Sharp & Dohme Corp. | PARTIAL INSULIN RECEPTOR AGONISTS AND GLP-1 ANALOGUES |
| US10689430B2 (en) | 2016-05-25 | 2020-06-23 | Merck Sharp & Dohme Corp. | Insulin receptor partial agonists |
| RU2764197C1 (ru) | 2016-09-23 | 2022-01-14 | Ханми Фарм. Ко., Лтд. | Аналоги инсулина с пониженной аффинностью к рецептору инсулина и их применение |
| MY200047A (en) | 2016-11-21 | 2023-12-06 | Univ Case Western Reserve | Rapid-acting insulin analogues of enhanced stability |
| AR111341A1 (es) | 2017-03-23 | 2019-07-03 | Hanmi Pharm Ind Co Ltd | Un conjugado del análogo de insulina con afinidad reducida para el receptor de insulina y uso del mismo |
| WO2018213151A1 (en) | 2017-05-18 | 2018-11-22 | Merck Sharp & Dohme Corp. | Pharmaceutical formulation comprising incretin-insulin conjugates |
| CN111032685A (zh) | 2017-08-17 | 2020-04-17 | 诺沃挪第克公司 | 新型酰化胰岛素类似物及其用途 |
| CN114144426A (zh) * | 2019-04-19 | 2022-03-04 | 印地安纳大学理事会 | 餐时或基础胰岛素类似物通过内部二硒桥的稳定化 |
| TWI844709B (zh) | 2019-07-31 | 2024-06-11 | 美商美國禮來大藥廠 | 鬆弛素(relaxin)類似物及其使用方法 |
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| US4450150A (en) | 1973-05-17 | 1984-05-22 | Arthur D. Little, Inc. | Biodegradable, implantable drug delivery depots, and method for preparing and using the same |
| US4275152A (en) | 1977-02-03 | 1981-06-23 | Eastman Kodak Company | Hydrolysis of protein-bound cholesterol esters |
| PH25772A (en) | 1985-08-30 | 1991-10-18 | Novo Industri As | Insulin analogues, process for their preparation |
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2011
- 2011-06-16 EP EP11796430.4A patent/EP2582719B1/en not_active Not-in-force
- 2011-06-16 JP JP2013515513A patent/JP5969469B2/ja not_active Expired - Fee Related
- 2011-06-16 AU AU2011268327A patent/AU2011268327B2/en not_active Ceased
- 2011-06-16 WO PCT/US2011/040699 patent/WO2011159895A2/en not_active Ceased
- 2011-06-16 US US13/701,146 patent/US8940860B2/en not_active Expired - Fee Related
- 2011-06-16 CN CN201180039321.7A patent/CN103068842B/zh not_active Expired - Fee Related
- 2011-06-16 CA CA2802485A patent/CA2802485C/en not_active Expired - Fee Related
-
2014
- 2014-12-08 US US14/563,362 patent/US9458220B2/en active Active
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2016
- 2016-08-05 US US15/229,942 patent/US10233225B2/en not_active Expired - Fee Related
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